Aim of the study was to investigate the effect of transdermal fentanyl (TDF) as an adjuvant to paravertebral block (PVB) for pain control after breast cancer surgery.

Trial included 50 females scheduled for mastectomy that were randomly allocated into one of two equal groups. The transdermal (TDF group) used transdermal fentanyl patches (TFPs) 25 mcg per hour applied 10 hours preoperative, then PVB with 20 ml of bupivacaine 0.25% was done before induction of general anesthesia. The PVB group used placebo patches in addition to PVB. Postoperative pain was assessed with a visual analog scale (VAS) score up to 48 hours. IV morphine 0.1 mg/kg was given when the VAS is ≥ 3 or on patient request. There was no significant difference between the two groups regarding age, weight, ASA class, and duration of anesthesia and surgery. The primary outcome measures were the time to first request for analgesia and the total analgesic consumption in the first 48 hours.

• N: 50  
• AGE: 49.8 (SD = 3.5) 
• FEMALES: 100%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Breast cancer

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Egypt

PHASE OF CARE: Active anti-tumor treatment

Randomized, double-blind trial

Time to first request for analgesia and total analgesic consumption in the first 48 hours were analyzed. Group differences were compared using the independent samples Student's t-test or Mann-Whitney for numerical variables. Chi-square test was used to examine the relationship between qualitative variables. Two-way analysis of variance was used to test the interaction between the two groups' hemodynamic variables. Observer’s Assessment of Alertness/Sedation (OAA/S) and the visual analog scale (VAS) were also used.

The VAS score was significantly lower in TDF group than PVB group from 30 minutes postoperatively up to 24 hours. The time to the first request of additional analgesia was significantly longer in the TDF group (p < 0.001). The total dose of morphine consumption in 48 hours was significantly lower in TDF group (p = 0.039)

The use of fentanyl patches preoperatively and BVP appears to reduce the amount of morphine requested within the first 48 hours postoperatively for breast surgery and correlate with lower VAS scores.

Small sample (< 100)

Preemptive analgesia, if TFP is applied before surgery, it can be used to relieve postoperative pain.

To evaluate the efficacy and tolerability of high-dose oxycodone-naloxone (OXN-PR) in chronic cancer pain.

Patients aged 18 years or older with chronic cancer pain of moderate to severe intensity on analgesic therapy and/or who were intolerant to pain medications due to gastrointestinal side effects were switched to OXN-PR. Intensity of pain was measured on a 0 to 10 numerical rating scale. Patients were prescribed oral OXN-PR for pain control at the first visit with doses equivalent to morphine dosage. All patients were evaluated by trained clinicians at baseline and after 14, 30, 45, and 60 days. Components of the evaluation included quality of life, symptoms of constipation, and safety evaluations.

• N: 119 entered; 101 final  
• AGE: 28-94 years old (median = 64 years) 
• MALES: 61.3%  
• FEMALES: 38.7% 
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Pulmonary, GI, and GU cancers. 
• OTHER KEY SAMPLE CHARACTERISTICS: 91.6% with metastatic disease; 75.6% with bone involvement.

• SITE: Multi-site (seven pain centers)   
• SETTING TYPE: Outpatient    
• LOCATION: Italy

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Elder care, palliative care

Multicenter, prospective 60-day observation on consecutive patients with cancer with uncontrolled moderate to severe chronic pain or intolerant to other analgesics.

Brief Pain Inventory Short Form 7; Bowel Function Index; 0- to 10-point safety evaluation.

At 60 days, 18 (15.1%) of patients had prematurely discontinued the OXN-PR due to death, disease progression, major side effects, lack of efficacy, or personal reasons. OXN-PR was associated with reduction in acute pain intensity compared to baseline at all measurement intervals (p = 0.009). A lower response rate was found in patients without metastatic disease. Bowel function improved after OXN-PR (p < 0.0001). There was also a significant decline in patients utilizing laxatives/enemas. The number of other side effects, such as nausea, somnolence, dizziness, tremors, or confusion was decreased by nearly 50% (p < 0.001).

OXN-PR agonist-antagonist combination was highly effective in managing cancer-related pain, reduced bowel dysfunction, and minimized opioid side effects.

• Risk of bias (no control group)
• Other limitations/explanation: Relatively small final sample size of 101 patients.

Oxycodone-naloxone is an effective therapy for the management of patients with cancer-related pain who may be intolerable to other therapies.

To establish whether the analgesic effect of morphine improves in patients with cancer when administered in combination with magnesium

Patients with moderate or severe cancer pain and starting morphine were randomized to 656.6 mg sulfate BID or placebo.

• N: 40   
• AGE: Mean = 58.5 years in intervention group and 58.2 years in the placebo group
• MALES: 22 (55%)
• FEMALES: 18 (45%)
• KEY DISEASE CHARACTERISTICS: Not stated
• OTHER KEY SAMPLE CHARACTERISTICS: Only gender, age, height, and weight were reported. No information on current treatment

• SITE: Not stated/unknown   
• SETTING TYPE: Not specified    
• LOCATION: Not specified

PHASE OF CARE: Not specified

Prospective, randomized, double-blind trial

Pain intensity measured on 0 to 10 scale at baseline and weeks 1, 2, 3, and 4. Functional performance as assessed by Karnofsky and QOL assessed by the EORTC at first and last interview. Dose of morphine and side effects were recorded.

No difference in participant characteristic, pain intensity, morphine dose, functional performance, or QOL. Pain intensity was significantly reduced in both groups. No difference was found in the side effects of morphine except for constipation in week 1.

Morphine combined with magnesium did not lead to better analgesic effects, QOL, or functional performance.

• Small sample (< 100)
• Risk of bias (sample characteristics)
• Selective outcomes reporting
• Other limitations/explanation: Minimal details on study population

The use of morphine and magnesium did not induce a better analgesic effect or improve functional status or QOL.

To test the intelligent pain management system (IPMS) on mobile phones among patients with cancer with pain.

Data regarding pain assessments, satisfaction, and effectiveness of pain management, and change in QOL was recorded through a mobile phone app, the IPMS.

• N = 46   
• MEAN AGE: Trial group, 76 years; control group, 68 years
• MALES: 70%  
• FEMALES: 30%
• CURRENT TREATMENT: Chemotherapy, other: Not specified which type of treatment. Not radiation-exclusion criteria.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Oncology Center of Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch, China

PHASE OF CARE: Active anti-tumor treatment

Randomized controlled trial

• Karnofsky Performance Status (KPS)
• Pain Management Knowledge
• Paon Assessment

Over the 14-day trial period, the trial group had on a score of on average 0.28 less than the control group (p < 0.001) and at the end of the trial period, 0.75 less than the control group (p < 0.001).

IPMS use as a way to assess pain in patients with cancer has shown promising results. A larger study with a variety of patients with cancer is needed to assess for generalizability.

• Small sample (< 100)
• Baseline sample/group differences of import
• Key sample group differences that could influence results
• Other limitations/explanation: Short duration of the trial period

Using technology such as mobile device apps can be a novel way to maintain constant contact and management of patient pain. It is worthwhile to invest resources in expanding research in this area.

STUDY PURPOSE: The purpose of this systematic review of the literature was to determine the impact of hypnosis on the most common symptoms patients with cancer experience at the end-of-life: fatigue, sleep disturbances, pain, appetite loss, and dyspnea.

TYPE OF STUDY: Systematic review

DATABASES USED: EMBASE, MEDLINE, COCHRANE, PsycINFO, and SCOPUS

YEARS INCLUDED: From inception through November 2016

INCLUSION CRITERIA: Published in peer-reviewed journal; English language; RCT methodology and efficacy data; assessed at least one of five symptoms: fatigue, sleep disturbances, pain, appetite loss, or dyspnea; included hypnosis intervention; included patients with cancer at end-of-life 

EXCLUSION CRITERIA: Not stated

TOTAL REFERENCES RETRIEVED: 94

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: None of the studies met the inclusion criteria

FINAL NUMBER STUDIES INCLUDED: 0

TOTAL PATIENTS INCLUDED IN REVIEW: 0

SAMPLE RANGE ACROSS STUDIES: 0

KEY SAMPLE CHARACTERISTICS: None

PHASE OF CARE: Not specified or not applicable

Results from this systematic review revealed no studies were identified that rigorously tested hypnosis as an intervention to improve five of the most common symptoms experienced by patients with cancer at end-of-life. A review of 100 abstracts revealed that none of the identified studies met the inclusion criteria. These results were consistent with previous research that failed to identify RCTs using hypnosis for management of sleep disturbances, fatigue, pain, appetite loss, or dyspnea in terminally ill patients with cancer (Rajasekaran et al., 2005).

Patients with cancer at the end of life commonly experience a multitude of challenging symptoms, specifically, sleep disturbances, fatigue, pain, appetite loss, and dyspnea. Management of these symptoms at end of life is a key part of care and finding interventions to relieve them is a National Institutes of Health (NIH) priority. Although hypnosis proved to be effective in improving symptoms in patients with cancer and other chronic illnesses, hypnosis has not been rigorously studied for symptoms in patients with cancer at the end of life.

Limited number of studies included

The future of hypnosis for improving symptom in patients with cancer at the end of life is promising. However, as a result of the current lack of rigorous research on hypnosis for symptom management in patients with cancer at the end of life, hypnosis cannot be recommended.

To evaluate the effectiveness of epidural analgesia after LDG

Patients received either combined thoracic epidural  and general analgesia or general anesthesia alone.

• N = 95 (84 enrolled in the analysis)
• AGE: Mean = 66.1 (SD = 13.4) in the epidural group; mean = 66.4 (SD = 10.7) in the non-epidural group
• MALES: 71% in the epidural group, 70% in the non-epidural group  
• FEMALES: 26% in the epidural group, 30% in the non-epidural group
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Previously untreated gastric cancer

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Osaka University

PHASE OF CARE: Active anti-tumor treatment

Retrospective study of 84 patients with previously untreated gastric cancer who underwent LDG; received either combined thoracic epidural and general anesthesia or general anesthesia alone. Data was recorded on the patients, surgery, postoperative outcomes, and anesthesia-related complications.

The following data was collected: sex, age, body mass index, American Society of Anesthesiologists (ASA) anesthetic risk classification, previous laparotomy, tumor stage, lymph node dissection, reconstructive procedure, length of surgery, blood loss, postoperative complications above grade 2 in Clavien-Dindo classification, number of additional doses of analgesics required during the first three days after surgery, first day of oral intake, first day of flatus, first day of ambulation, length of hospital stay, and incidence of anesthesia-related complications such as nausea, vomiting, hypotension, bradycardia, and urinary retention.

The two groups were not significantly different with regard to the first day of ambulation, first day of oral intak,e or length of hospital stay. The epidural group experienced a significantly earlier first day of flatus and required significantly fewer additional postoperative analgesic doses compared to the non-epidural group. One patient in the epidural group experienced a urinary tract infection, which was cured with antibiotics; nevertheless, the groups did not have significantly different rates of urinary tract infection.
There was no significant differences between the epidural group and the non-epidural group in the degree of nausea, vomiting, hypotension, or bradycardia. However, significantly more (20.6%) cases of postoperative urinary retention were observed in the epidural group than the non-epidural group. Adverse events related to epidural anesthesia, such as nausea, hypotension, and bradycardia, resolved after a brief interruption or dose reduction of the epidural anesthesia.

The optimal postoperative analgesic regimens for laparoscopic gastrectomy have not yet been determined. Our findings suggest that epidural anesthesia could lead to a decreased use of additional analgesics after LDG. However, as found in previous reports, epidural anesthesia was associated with a higher risk of urinary retention.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Findings not generalizable
• Subject withdrawals ≥ 10%

None included

To compare the pain scores and complications of patients who underwent cytoreductive surgery for ovarian cancer and used either patient-controlled epidural analgesia (PCEA) or patient-controlled IV analgesia (PCA) for postoperative pain management

Use of either patient-controlled epidural analgesia (PCEA) or patient-controlled IV analgesia (PCA) for postoperative pain management in ovarian cancer surgery

• N = 105
• AGE: Mean = 53.8 years (SD = 8.1) in PCEA; mean = 53.3 years (SD = 11.3) in PCA
• MALES: Not noted  
• FEMALES: Not noted
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Patients undergoing laparotomy for ovarian cancer

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Center for Uterine Cancer in the National Cancer Center of Korea

PHASE OF CARE: Active anti-tumor treatment

Retrospective review of pain scores for postoperative days (POD) 0-5 and the incidence of complications were examined and compared in patients receiving PCEA and PCA.

Numeric rating scale was used to measure differences in intensity of pain

Of 105 patients, 38 received PCEA and 67 received PCA. Pain scores were significantly lower in the PCEA group than the PCA group at POD 0, 1, and 3 and tended to be lower in the PCEA group at PODs 2, 4, and 5. PCEA provided significantly better pain relief as analyzed by a mixed-effect model.

PCEA was more effective for postoperative pain management compared with PCA from POD 1 to POD 3 in patients with ovarian cancer who underwent cytoreductive surgery, without increased morbidity.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Findings not generalizable
• Subject withdrawals ≥ 10%

None included

To evaluate the effect of acupressure in managing pain experienced by patients with cancer with bone metastases

Study participants received a 10 minute acupressure session prior to each radiotherapy treatment for a total of eight sessions. Acupressure was applied for up to 10 seconds to 31 points on the body surface for approximately 5 minutes total. Acupressure is delivered by applying physical pressure and is believed to provide energy circulation and balance in the body.

• N = 60 
• AGE: Mean = 57.7 years (range = 20-60)
• MALES: 67%  
• FEMALES: 33%
• CURRENT TREATMENT: Radiation
• KEY DISEASE CHARACTERISTICS: Most frequent cancer type was respiratory (n = 21), followed by breast, urinary, reproductive, digestive, and leukemia.
• OTHER KEY SAMPLE CHARACTERISTICS: Only 31 participants had metastatic cancer, and it is unclear how many actually had bone metastases.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Radiotherapy unit of an institution in Turkey.

PHASE OF CARE: Active anti-tumor treatment

Non-randomized controlled trial

Pain level was measured using a visual analog scale at baseline and after the 8 acupressure sessions. In addition, participants completed a questionnaire at baseline which collected sociodemographic and disease-related information.

The difference in the intervention group’s mean pain score from baseline (7.6, SD = 1.9) and after acupressure (6.8, SD = 1.9) was statistically significant (p = 0.004) compared to the control group’s pain level (baseline = 8.2, SD = 1.7; after acupressure = 7.7, SD = 2.1; p = 0.056).

Although a statistically significant difference in pain level was found for the intervention group, it cannot be concluded that acupressure is effective in reducing pain in patients with cancer with bone metastases. Due to the limitations identified below and since only 31 of the 60 study participants had metastatic cancer, rigorous testing of this intervention needs to be conducted before acupressure can be recommended for practice in patients with bone metastases.

• Small sample (< 100)
• Risk of bias (no blinding) 
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)
• Findings not generalizable
• Other limitations/explanation: Findings are not generalizable due to the small sample size, mixed sample of metastatic and non-metastatic cancers, and it is unclear if those with metastatic cancer actually have bone metastases. 
• The authors measured pain at the end of study rather than after each acupressure session. It would have been helpful to learn if acupressure has an immediate effect in this patient population.

Although this study did not provide scientific evidence for the use of acupressure in managing bone metastases, side effects are rare and the benefits of acupressure outweigh harms. If both the clinician and patient agree that this is an appropriate intervention for managing pain, nurses should know who to refer the patient to for acupressure treatment. In addition, acupressure appears to be an intervention which nurses could learn with brief training.

To compare outcomes between women receiving the tolerable upper limit intake of vitamin D3 to those receiving recommended dietary allowances.

Patients were randomized to receive either usual recommended dose or 4,000 IU vitamin D3 and 1,000 mg calcium carbonate. Participants had a four-week run-in period with 600 IU to normalize serum levels, and then received treatment according to random assignment. Treatment was given for six months. Adherence was determined by pill counts at study visits and symptoms were monitored through weekly diaries.

• N = 113   
• AGE: Mean = 60.9 years (SD = 8.8)
• FEMALES: 100%
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Breast cancer receiving aromatase inhibitors and experiencing AIMSS
• OTHER KEY SAMPLE CHARACTERISTICS: Patients had been on AI treatment an average of 19.9 months, and 54% had prior chemotherapy.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Minnesota

PHASE OF CARE: Late effects and survivorship

Double-blind RCT

• Australian/Canadian osteoarthritis hand index
• Western Ontario and McMaster osteoarthritis index (WOMAC)
• Breast cancer trial symptom scale-musculoskeletal subscale (BCPT-MS)
• Handgrip strength
• Serum hormone and 25(OH)D levels
• Use of analgesics

In the intervention group, serum total and free 25(OH)D levels increased (p < 0.0001).  After six months, there were no differences in outcome measurement scores between groups.

High-dose vitamin D3 did not results in improvement in AI-related musculoskeletal symptoms.

No information on use of analgesics is provided

This study did not show an effect of high-dose vitamin D3 for musculoskeletal side effects associated with AI treatment.

To directly compare fentanyl sublingual tablets (FST) and subcutaneous morphine (SCM) in the first 30 minutes of a severe breakthrough pain episode.

Patients were randomly assigned to receive FST or SCM. Placebo was saline solution or a sublingual tablet reproducing the fentanyl preparation. Re-medication was available after 30 minutes for patients who did not achieve at least a 2-point reduction in pain. Average pain scores were obtained at baseline, 10, 20, 30, and 60 minutes. SCM was given at a 5 mg dose, and the dose for FST was 100 mcg. A non-inferiority margin of 1 point on the pain scale was used.

• N = 113   
• AGE: Mean = 60 years (range = 23-88)
• MALES: 48.7%  
• FEMALES: 51.3%
• KEY DISEASE CHARACTERISTICS: Multiple tumor types; GI and urogenital were most common
• OTHER KEY SAMPLE CHARACTERISTICS: Current pain of 6 or greater on a 1 to 10 numeric pain scale. Well-controlled background pain for previous 24 hours. Median pain intensity was 7.5 in both groups.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Italy

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care

Double-blind, double dummy, noninferiority RCT

Numeric rating scale

Overall there was no significant difference in change of pain intensity between groups; however, non-inferiority of FST was not shown because the difference between groups was less than the margin established for testing. Patients tended to prefer the tablet rather than subcutaneous injection.

Subcutaneous morphine showed slightly better efficacy than the fentanyl tablet for reducing breakthrough pain intensity. Both approaches were effective.

Risk of bias (no blinding)

This study showed that both fentanyl sublingual tablets and subcutaneous morphine were effective in reducing the intensity of breakthrough pain. Findings here showed slightly better efficacy of the subcutaneous morphine, though patients preferred the tablet.